rs200973220

Variant names:

• chr19-46623616-C-T
• rs200973220
• NM_000960.4:c.610G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-46623616-C-T
• chr19-46623616-C-A
• chr19-46623616-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000960.4(PTGIR):​c.610G>A​(p.Gly204Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,549,754 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: PTGIR NM_000960.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46
• Publications: 3 publications found

Genes affected

PTGIR (HGNC:9602): (prostaglandin I2 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor family 1 and has been shown to be a receptor for prostacyclin. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023366123).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000960.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGIR	NM_000960.4	MANE Select	c.610G>A	p.Gly204Ser	missense	Exon 2 of 3	NP_000951.1	P43119

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGIR	ENST00000291294.7	TSL:1 MANE Select	c.610G>A	p.Gly204Ser	missense	Exon 2 of 3	ENSP00000291294.1	P43119
	PTGIR	ENST00000872951.1		c.610G>A	p.Gly204Ser	missense	Exon 2 of 3	ENSP00000543010.1
	PTGIR	ENST00000872954.1		c.610G>A	p.Gly204Ser	missense	Exon 2 of 3	ENSP00000543013.1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000338 AC: 50 AN: 148078 AF XY: 0.000315

Gnomad AFR exome AF: 0.000252

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00167

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000449 AC: 628 AN: 1397378 Hom.: 1 Cov.: 31 AF XY: 0.000441 AC XY: 304 AN XY: 689638

African (AFR) AF: 0.0000630 AC: 2 AN: 31740

American (AMR) AF: 0.000335 AC: 12 AN: 35816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35940

South Asian (SAS) AF: 0.0000756 AC: 6 AN: 79388

European-Finnish (FIN) AF: 0.00222 AC: 102 AN: 45902

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5690

European-Non Finnish (NFE) AF: 0.000441 AC: 476 AN: 1079730

Other (OTH) AF: 0.000500 AC: 29 AN: 58006

GnomAD4 genome AF: 0.000446 AC: 68 AN: 152376 Hom.: 0 Cov.: 33 AF XY: 0.000470 AC XY: 35 AN XY: 74520

African (AFR) AF: 0.0000481 AC: 2 AN: 41594

American (AMR) AF: 0.000980 AC: 15 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000383 Hom.: 0

Bravo AF: 0.000400

ESP6500AA AF: 0.000241 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000236 AC: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.086
Sift	Benign	0.44	T
Sift4G	Benign	0.44	T
Polyphen		0.13	B
Vest4		0.15
MVP		0.85
MPC		0.18
ClinPred		0.015	T
GERP RS		3.7
Varity_R		0.14
gMVP		0.67
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200973220; hg19: chr19-47126873;